Parkinsons and Epilepsy Flashcards
Parkinsons disease
Neurodegenerative disorder consisting of loss of dopaminergic neurones in the substantia nigra leading to degeneration of projections
1% incidence, increases with age and male gender
PC - bradykinesia, resting tremor, rigidity and postural instability. Autonomic symptoms of postural hypotension, urinary incontinence, constipation and erectile dysfunction
1st symptoms = anosmia, depression/anxiety, sleep disturbance,
Parkinsonism
Clinical signs and symptoms of PD may be caused by MSA, huxngtingtons or small vessel ischemia
Sites for medication to act in PD
Levodopa - replaces missing dopamine
Monoamine oxidase inhibitors - prevent dopamine breakdown
Dopamine agonists - mimic dopamine actions by binding to the post synaptic receptor
COMT inhibitors - prevent breakdown at synaptic cleft
L-dopa (madopar = co-careldopa) MOA
Precursor for dopamine given with decarboxylase inhibitor to prevent its breakdown peripherally. Without this only 5% would reach the brain and SE of dopamine peripherally would be N/V, arrhythmias and postural hypotension
Short term SE L-dopa
N/V, reduced appetite
Somnolence, insomnia and vivid dreams
Postural hypotension - vasodilation of cardiac vessels
Long term SE L-dopa
Motor compilations 50% pt @ 5 years = wearing off of dose requiring increase strength preparations, on off switching and freezing
Dyskinesia = continual writhing, rocking or fighting movements. Dose related. To reduced effects take with meals, small frequent doses and use adjunct medications
CI L-dopa
Heart failure, arrhythmias. Closed angle glaucoma
Interactions of L-dopa
MAOI’s increased risk of hypertensive crisis
Antihypertensives = increased effect
Warn pt about driving or operating heavy machinery due to drowsiness or dyskinesia
Don’t abruptly stop taking medication = rhabdomyolysis or neuroleptic malignant syndrome
Dopamine agonists (Ropinerole or rotigotine)
Mimics effect of dopamine by binding to post synaptic receptors in striatum. Not used in elderly due to reduced efficacy compared to L-dopa and can have increased psychotic effects
1st line in patients <70y/o newly diagnosed
SE of dopamine agonists
Somnolence, confusion and hallucinations
N/V and reduced appetite
Impulse control disorders 15% hyper sexuality, gambling, shopping sprees
CI drugs in PD
Dopamine antagonists = haloperidol
Mono-amine oxidase B inhibitors (Selegline/rasagiline)
Irreversibly inhibit MOAB the specific enzyme for dopamine breakdown after reuptake from the synaptic cleft
Used as an adjunct to L-dopa
SE of MAOBi
N/V, confusion and insomnia, postural hypotension
Increase risk of serotonin syndrome
Catechol-O-methyl-tranferase inhibitors (Entacapone)
Inhibit COMT, this enzyme is responsible for breakdown of dopamine at the synaptic cleft. Prolongs its action at the post synaptic receptor
SE COMT
Increased risk of dyskinesias, diarrhoea, reddish brown urine. Tolcapone is more effective but increased risk of hepatotoxcity
Amantidine
Acts as a minor antimuscarinic, stimulating dopamine release and inhibiting its reuptake. Can reduced dyskinesia
SE = ankle oedema, postural hypotension and confusion
Treatment of PD 50-60y/o and >70y/o
<70y/o and new diagnosis = MAOI and dopamine agonists. L-dopa sparing strategy
> 70y/o / comorbidities = L-dopa +/- MAOBi or COMT
If severe dyskinesia reduce dose of L-dopa and start amantadine
Mx PD complications
Anxiety/ insomnia = CBT, SSRI’s, Zopiclone
Constipation = hydration, laxatives
Nocturne and incontinence = catheter?
Drug induced Parkinsons
Dopamine antagonists = haloperidol, metacloprimide
Lithium, sodium valproate, fluoxetine
Hypertensive emergency vs Hypertensive crisis
Emergency = High blood pressure and acute impairment of 1+ organ systems
Hypertensive crisis = BP >180 no evidence of organ damage
PC hypertensive emergency and Mx
Retinal haemorrhages and papilloedema
increased ICP = headache, vomiting, low GCS,
Acute renal failure = haemturia and proteinuria
Mx IV sodium nitroprusside
Complications of HTN emergency
Hypertensive encephalopathy, CVA, inter cranial haemorrhage. MI, LV dysfunction, AKI
Causes of HTN emergency
Pregnancy, cocaine, Phaechromocytoma, head trauma, dopamine agonist, MAOI, renal artery stenosis
Epilepsy and seizures definition
Epilepsy = predisposition to having seizures Seizure = A clinical symptom caused by abnormal electrical discharge in the brain
Generalised seizures
Loss of consciousness, discharge over the entire cortex
Include absence seizures, tonic-clonic, myoclonic
Mx = sodium valproate
Partial seizures
Focal onset, consciousness maintained
Simple and complex - then can turn into generalised seizures
Often demonstrate automatism seen due to activity at temporal lobe = smacking of lips, chewing, clapping of hands. Can include olfactory hallucinations
Mx = carbamazepine
Causes of epilepsy
Congenital - cerbral palsy, idiopathic, head injury, post stroke or meningitis
Guide to epilepsy Mx
Antiepileptics prescribed after 2x distinct episodes
Monotherapy unless treatment resistant
Never withdraw abruptly
Seizure of any type inform DVLA
Causes of Seizures
Vascular = stroke, SAH Infections = sepsis, meningitis, encephalitis Trauma = head injury Metabolic = hypoglycemia, hypo/hyperthermia, electrolyte abnormalities, hypoxia Inflammatory = amyloidois, alzheimers Neoplastic = SOL Doctors = drugs cocaine, MDMA, alcohol,
Sodium Valproate MOA
Valproate acts on Na+, Ca2+ channels and GABAa receptors. It inhibits GABA transaminase therefore increasing GABA level leading to neuronal inhibiton
Sodium Valproate uses
1st line for idiopathic generalised epilepsy, myoclonic and absent seizures
SE sodium valproate
wt gain, N/V, impaired glucose tolerance, tremor
Highly teratogenic don’t use in pregnancy
Can = acute liver failure monitor LFT’s 6 monthly
thrombocytopenia
pancreatitis
Hyperammonemia = risk of encephalopathy
Interactions of sodium valproate
CYP450 inhibitor = increased effect of warfarin, theophylline, lamotrigine
Ethosuximide
Blocks specific Ca2+ channels that are active in generalised seizures. Used 1st line for children with absent seizures
Drugs to avoid in absent/myoclonic seziures
Carbamazepine, phenytoin, gabapentin and pregabalin
SE of ethosuximide
GI upset, eosinophilia, potentiation of tonic clonic seizures
Carbamazepine MOA
Blocks voltage gated Na+ channels reducing membrane excitability preventing the propagation of action potentials. Opens K+ channels promoting GABA release.
Carbamazepine 1st line
All partial seizures and trigeminal neuralgia
SE Carbamazepine
Skin reaction and rash, can = SJS
Dose related = ataxia, diplopia and vertigo/dizziness
Osteomalacia and folate defence
leukopenia and thrombocytopenia
Interactions of carbamazepine
Enzyme inducer - can induce its own metabolise soma need to gradually be titrated up during initial weeks of Mx
CYP450 inhibitors
Sodium valproate, isoniazid, macrolides amiodarone, SSRI, quinolones, PPI, grapefruit
CYP450 inducers
Carbamazepine, phenytoin, theophylline, rifampicin, ST johns wart
Phenytoin MOA
Blocks propagation of action potentials by preferentially blocking excitation of neurones that are repeatedly firing. Discourages spread not initiation. Acts on Na+ channels
Enzyme inducer so dose may need to be titrated up, reduces effective dose of other drugs
Uses of phenytoin
Status epileptics and myotonic dystrophy
SE of phenytoin
Narrow therapeutic window so can = toxicity
gingival hypertrophy due to inhibition of collagen catabolism. Acne, hirsutism, insomnia, peripheral neuropathy, tremor, dyskinesia
Macrocytic anaemia due to increasing folate metabolism, osteomalacia due to increased vit d metabolism
Screening of chinese/thai on phenytonin
HLAB-1502 gene which gives a increased incidence of SJS
Acute phenytoin toxicity PC
Severe cerebellar signs - ataxia, diplopia, dysmetria, nystagmus, dysdokinesia
Drowsiness, needs cardiac and BP monitoring
IV phenytoin may - hypotension, arrhythmias, cardiac and rep depression
CI to phenytonin
Teratogenic, HLAB-1502 +ve, heart block
Lamotrigine MOA
Stabilises pre-synaptic neuronal membranes by blocking voltage gated Na+ and Ca2+, reducing the release of glutamate and excitatory neurotransmitter
Alternative for generalised and partial epilepsy safest in pregnancy!
SE lamotrigine
Increased incidence of SJS and TEN, 10% of people experience a rash (start low and increase dose gradually)
GI disturbance
Stop if signs of rash, monitor LFT’s and FBC
Levertircetam
Future drug of choice. Inhibits synaptic vesicle protein 2A reducing vesicle recycling and inhibiting presynaptic Ca2+ channels
Well tolerated, few drug interactions. Renally excreted
SE Levertircetam
labile mood, somnolence, behavioural disturbance and psychosis
COCP and antiepileptics
Reduced efficacy of COCP = carbamazepine, phenytoin
COCP reduces the efficacy of lamotrigine
Use increased strength COCP 50micrograms or mirena coil as alternative
Benzodiazepines (diazepam/midalozam) MOA
Agonists to the benzodiazepam receptor on GABA receptor complex. High affinity for GABA receptor bind causing Cl- channels to open hyperpolarising the membrane preventing further excitation.
Uses of benzodiazepines
Status epilepticus, alcohol withdrawal - seizures prophylaxis, sedation, short terms anxiety relief
SE benzodiazepines
Confusion, amenesia, hypotension
Can = respiratory depression
If long term lead to dependence
If overdose = IV flumazenil
Status epilepticus
5+ minutes of seizure activity or several recurrent seizures in 30mins
Mx status epilepticus
ABCDE - protect airway. Check glucose = hypoglycaemia is a common cause of seizures
IV lorazepam 0.07mg/kg stat
Alternatives in community = PR diazepam or buccal midolozam
If no improvement in 20mins IV phenytoin 15mg/kg, monitor BP, HR, ECG. Inform ITU
Sudden unexpected death epilepsy risk factors
Young age, poor control/compliance, generalised tonic/clonic, unwitnessed seizures
Pregnancy and anti epileptics
High dose folic acid 5mg for all. Lamotrigine is the safest in pregnancy. Aim to give mono therapy at lowest possible dose.
Don’t prescribe valproate
Driving and seizures
With any seizure not due to a reversible cause i.e. alcohol, drugs or fever cease driving and inform DVLA immediately
1st unprovoked seizure = 6 month ban
Established epilepsy = 1 year seizure free
Wernickes encephalopathy
Triad of ataxia, confusion and opthalmeplegia - nystagmus. Due to thiamine deficiency seen commonly in alcoholics
Korsakoff psychosis
Anterograde and retrograde amnesia due to maxillary body infarction due to chronic thiamine deficiency. LTM is maintained. Occasionally confabulation
Delirium tremens
Alcohol is an inhibitory of the CNS, rapid withdraw leads to reduced GABA = mass overexcitation. Worse 2-3 days post withdrawal
Mx acute alcohol withdrawal
ABCDE + correct hypoglycaemia
2 x 500mg thiamine IV TDS
IV chlordiazepoxide
PC Delirium tremens
Confusion, agitation, visual and auditory hallucinations, sweating, tachycardia, hyperthermia, tremors, N/V
Can lead to generalised tonic-clonic seizures.
O/E = high HR and BP, pyrexial, tremor, nystagmus, reduced GCS
Antiepileptic hypersensitivity
Rare but fatal complication linked to carbamazepine, lamotrigine and phenytoin. Symptoms 1-8 wks post exposure.
PC = fever, rash, lymphadenopathy, liver dysfunction, renal failure
